Sustained release drug formulations containing a carrier peptide

Abstract

The invention features a method of administering one or more therapeutic agents to a patient and delivering said agent or agents continuously over an extended period of time, said method comprising: obtaining a pharmaceutical composition including a peptide carrier, one or more therapeutic agents, and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier; and parenterally administering said pharmaceutical composition to a subject by injection, wherein said composition automatically forms a gel after interaction with the patient's bodily fluids and releases said peptide carrier and said agent or agents continuously within the patient over an extended period.

1. A sustained-release pharmaceutical composition for parenteral administration to a subject, comprising a carrier peptide comprising somatostatin or lanreotide, or a salt thereof, and one or more therapeutic agent(s) comprising a biologically active LHRH analogue, a dopamine agonist or a dopamine antagonist, or a salts thereof, wherein said composition automatically forms a gel after interaction with said subject's bodily fluids, said gel releasing both the carrier peptide and the therapeutic agent(s) continuously within the patient over an extended period of time. 
     
     
       2. A semisolid, sustained-release pharmaceutical suspension for parenteral administration to a subject, said suspension consisting essentially of: (1) a carrier peptide comprising somatostatin or lanreotide, or a salt thereof, one or more other therapeutic agent(s) and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said carrier peptide and said monomeric carrier are soluble in aqueous solvents; and (2) an aqueous solvent in an amount less than 50 percent of the amount of solvent required to dissolve said carrier peptide, wherein said semisolid suspension automatically forms a gel after interaction with the subject's bodily fluids, said gel releasing both the carrier peptide and the other therapeutic agent(s) continuously within the patient over an extended period time. 
     
     
       3. The suspension of  claim 2 , wherein said amount of solvent is less than 10 percent of the amount of solvent required to dissolve said carrier peptide. 
     
     
       4. A sustained-release gel, said gel comprising a carrier peptide comprising somatostatin or lanreotide, or a salt thereof, one or more therapeutic agent(s) comprising a biologically active LHRH analogue, a dopamine agonist, or a dopamine antagonist, or a salts thereof, wherein the gel releases both the carrier peptide and the therapeutic agent(s) continuously within a patient over an extended period time. 
     
     
       5. The gel of  claim 4 , wherein said gel is in the form of a pharmaceutical solid. 
     
     
       6. The gel of  claim 5 , wherein said pharmaceutical further comprises a solvent in an amount less than 50 percent of the amount of solvent required to dissolve said carrier peptide and to provide said pharmaceutical composition with a semisolid consistency. 
     
     
       7. A method of administering a carrier peptide and one or more other therapeutic agent(s) to a subject and delivering both the carrier peptide and the other therapeutic agent(s) continuously over an extended period of time, said method comprising:
 obtaining a solid pharmaceutical composition consisting essentially of the carrier peptide, wherein the carrier peptide is selected from somatostatin or lanreotide, or a salt thereof, the other therapeutic agent(s), and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said carrier peptide and said monomeric carrier are soluble in aqueous liquids, and 
 parenterally administering said solid composition to the patient, wherein said solid composition automatically forms a gel after interaction with the subject's bodily fluids, said gel releasing both the carrier peptide and the other therapeutic agent(s) continuously within the patient over an extended period of time. 
 
     
     
       8. The method of  claim 7 , wherein said solid composition is administered intramuscularly, subcutaneously, or intradermally. 
     
     
       9. The method of  claim 7 , wherein said solid composition comprises no monomeric carrier. 
     
     
       10. The method of  claim 7 , wherein the monomeric carrier is mannitol, sorbitol, or lactose. 
     
     
       11. The method of  claim 7 , wherein said solid composition is in the form of a cylinder with a diameter of less than 3 mm. 
     
     
       12. The method of  claim 7 , wherein said gel releases said carrier peptide continuously over a period of at least 14 days. 
     
     
       13. The method of  claim 7 , wherein said gel releases said other therapeutic agent(s) continuously over a period of at least 14 days. 
     
     
       14. A method of administering a carrier peptide and one or more therapeutic agent(s) to a subject continuously over an extended period of time, said method comprising obtaining a semisolid suspension comprising (1) the carrier peptide, wherein the carrier peptide comprises somatostatin or lanreotide, or a salt thereof, and the therapeutic agent(s), comprising a biologically active LHRH analog, a dopamine agonist, and a dopamine antagonist, or a salts thereof, and (2) an aqueous solvent in an amount less than 50 percent of the amount of solvent required to dissolve said peptide carrier and to provide said semisolid consistency; and
 parenterally administering said semisolid suspension to the subject, wherein said semisolid suspension automatically forms a gel after interaction with the subject's bodily fluids, said gel releasing both the peptide carrier and the therapeutic agent(s) continuously within the patient over an extended period of time. 
 
     
     
       15. The method of  claim 14 , wherein said amount of solvent is less than 10 percent of the amount of solvent required to dissolve said peptide carrier. 
     
     
       16. The composition of  claim 1 , comprising a therapeutic agent(s) comprising a dopamine agonist or antagonist, or a pharmaceutically acceptable salt thereof. 
     
     
       17. The composition of  claim 16  wherein said dopamine agonist is amantadine, bromocriptine, cabergoline, lisuride, mesulergine, pergolide, pramipexole, quinagolide, or ropinirole, or a pharmaceutically acceptable salt or analog thereof. 
     
     
       18. The composition of  claim 17  wherein said dopamine agonist is cabergoline, or a pharmaceutically acceptable salt thereof. 
     
     
       19. The suspension of  claim 2  or  3 , wherein the therapeutic agent(s) comprise a dopamine agonist or antagonist, or a pharmaceutically acceptable salt thereof. 
     
     
       20. The suspension of  claim 19  wherein said dopamine agonist is amantadine, bromocriptine, cabergoline, lisuride, mesulergine, pergolide, pramipexole, quinagolide, or ropinirole, or a pharmaceutically acceptable salt or analog thereof. 
     
     
       21. The suspension of  claim 20 , wherein said dopamine agonist is cabergoline, or a pharmaceutically acceptable salt thereof. 
     
     
       22. The sustained-release gel of  claim 4 ,  5 , or  6 , wherein the therapeutic agent(s) comprise a dopamine agonist or antagonist, or a pharmaceutically acceptable salt thereof. 
     
     
       23. The sustained-release gel of  claim 22  wherein said dopamine agonist is amantadine, bromocriptine, cabergoline, lisuride, mesulergine, pergolide, pramipexole, quinagolide, or ropinirole, or a pharmaceutically acceptable salt or analog thereof. 
     
     
       24. The sustained-release gel of  claim 23  wherein said dopamine agonist is cabergoline, or a pharmaceutically acceptable salt thereof. 
     
     
       25. The method of any one of  claim 7 ,  8 , or  9 - 13 , wherein the therapeutic agent(s) comprise a dopamine agonist or antagonist, or a pharmaceutically acceptable salt thereof. 
     
     
       26. The method of  claim 25  wherein said dopamine agonist is amantadine, bromocriptine, cabergoline, lisuride, mesulergine, pergolide, pramipexole, quinagolide, or ropinirole, or a pharmaceutically acceptable salt or analog thereof. 
     
     
       27. The method of  claim 26  wherein said dopamine agonist is cabergoline, or a pharmaceutically acceptable salt thereof. 
     
     
       28. The method of any one of  claim 14  or  15  wherein wherein the therapeutic agent(s) comprise a dopamine agonist or antagonist, or a pharmaceutically acceptable salt thereof. 
     
     
       29. The method of  claim 28  wherein said dopamine agonist is amantadine, bromocriptine, cabergoline, lisuride, mesulergine, pergolide, pramipexole, quinagolide, or ropinirole, or a pharmaceutically acceptable salt or analog thereof. 
     
     
       30. The method of  claim 29  wherein said dopamine agonist is cabergoline, or a pharmaceutically acceptable salt thereof. 
     
     
       31. A sustained-release pharmaceutical composition for parenteral administration to a subject, comprising a carrier peptide comprising somatostatin or lanreotide, or a salt thereof, and one or more therapeutic agent(s), wherein said composition automatically forms a gel after interaction with said subject's bodily fluids, said gel releasing both the carrier peptide and the therapeutic agent(s) continuously within the patient over an extended period of time wherein said composition further comprises a pharmaceutically acceptable, soluble, monomeric carrier, wherein said carrier peptide and said monomeric carrier are soluble in aqueous solvents, and the monomeric carrier is present in an amount of up to 30 percent, by weight, of the composition. 
     
     
       32. The composition of  claim 31 , wherein said composition further comprises an aqueous solvent, wherein the aqueous solvent is present in an amount less than 50 percent of the amount of solvent required to dissolve the carrier peptide. 
     
     
       33. A method of administering a carrier peptide and one or more therapeutic agent(s) to a subject continuously over an extended period of time, said method comprising obtaining a semisolid suspension comprising (1) the carrier peptide, comprising from somatostatin or lanreotide, or a salt thereof, and the therapeutic agent(s), and (2) an aqueous solvent in an amount less than 50 percent of the amount of solvent required to dissolve said peptide carrier and to provide said semisolid consistency; and
 parenterally administering said semisolid suspension to the subject, wherein said semisolid suspension automatically forms a gel after interaction with the subject's bodily fluids, said gel releasing both the peptide carrier and the therapeutic agent(s) continuously within the patient over an extended period of time wherein said semisolid suspension further comprises a pharmaceutically acceptable, soluble, monomeric carrier, wherein said carrier peptide and said monomeric carrier are soluble in aqueous solvents, and the monomeric carrier is present in an amount of up to 30 percent, by weight, of the composition. 
 
     
     
       34. The method of  claim 14 , wherein said composition further comprises an aqueous solvent, wherein the aqueous solvent is present in an amount less than 50 percent of the amount of solvent required to dissolve the carrier peptide. 
     
     
       35. The composition of  claim 1 , wherein the composition comprises triptoreline acetate as the therapeutic agent. 
     
     
       36. The composition of  claim 1 , wherein the composition comprises carbergoline as the therapeutic agent.